tbuckley/cabot-search huggingface dataset:
A phase II trial evaluating combination pemetrexed and avelumab in patients with MTAP-deficient advanced urothelial cancer.
Authors: Amishi Yogesh Shah, Matthew T Campbell, Rebecca Tidwell, Arlene O. Siefker-Radtke, Sangeeta Goswami, Omar Alhalabi, Ana Cecilia Adriazola, Leah Shaw, Yin Ye, Jianfeng Chen, Xinmiao Yan, Linghua Wang, Jianjun Gao
Journal: Journal of Clinical Oncology (2022)

TPS4612 Background: MTAP-deficiency occurs primarily due to homozygous loss in chromosome 9p21 and is seen in approximately 25% of urothelial cancers. MTAP-deficiency portends aggressive biology with poorer outcomes than in MTAP-proficient tumors; for example, in the IMvigor210 data, MTAP-deficient patients had median overall survival of 8.0 months, compared to 11.3 months in MTAP-proficient patients (p = 0.042). MTAP-deficient tumors lack salvage nucleotide synthesis pathways and thus are uniquely sensitive to anti-folate agents; however, in prior clinical work with pemetrexed in these tumors, responses are relatively short-lived. In-vivo data has suggested that pemetrexed can increase tumor infiltrating T-cells, macrophages, dendritic cells, and PD-L1 expression in MTAP-deficient tumors and decrease myeloid-derived suppressor cells (MDSCs). As such, it was postulated that sequential treatment with anti-folate chemotherapy (pemetrexed) and immune checkpoint inhibition (avelumab) would improve responses in MTAP-deficient urothelial cancer. Methods: A prospective phase II trial of patients with advanced MTAP-deficient urothelial cancer is being conducted under IRB-approved protocol NCT03744793. This study will enroll 25 patients at a single site (The University of TX, MD Anderson Cancer Center). Key eligibility criteria include patients with advanced MTAP-deficient urothelial cancer with measurable disease in second-line or beyond. MTAP-deficiency is confirmed with CLIA-approved IHC or NGS. Patients are stratified as being IO-pretreated versus IO-naïve. All patients receive a lead-in cycle of pemetrexed (500 mg/m2) followed by combination pemetrexed (500 mg/m2) and avelumab (10 mg/kg) IV every three weeks until disease progression, patient withdrawal, or unacceptable toxicity. Three biopsies per patient with tissue collection at trial baseline, on single agent pemetrexed, and on combination pemetrexed-avelumab are performed. The primary objective of this trial is to evaluate response rate with sequential pemetrexed and avelumab in MTAP-deficient urothelial cancer. Imaging response assessment is done via RECIST v1.1. Secondary objectives are to evaluate progression-free survival (PFS) and overall survival (OS), as well as to perform correlative studies evaluating the effect of this therapy on immune cells and tumor microenvironment. This correlative work includes but is not limited to evaluation of peripheral T-cells, tumor-infiltrating T-cells, macrophages, and MDSCs. Interim analyses for futility and safety occur in cohorts of 5 patients and are performed based on Bayesian sequential methods. Fifteen patients have been enrolled thus far. Clinical trial information: NCT03744793.
Primary site and survival in osteosarcoma: A National Cancer Database (NCDB) analysis.
Authors: Vincent Eaton, Connor Tupper, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2022)

e23512 Background: Osteosarcoma (OSC) is the most common primary bone tumor and typically affects the appendicular skeleton (specifically, the long bones of the upper and lower extremities). However, this cancer can affect other regions of the body as well, such as the skull, mandible, ribs, vertebral column, and other areas involving bone and/or any articular cartilage and, to the author’s knowledge, all possible primary sites have not been investigated. The aim of this study is to see whether or not the primary site of the tumor in OSC patients may have an effect on survival outcomes. Methods: Using the NCDB, patients diagnosed with OSC between 2004-2018 were identified using ICD-O-3 histology codes 9180 through 9193. The cohort was analyzed to investigate survival outcomes in different primary sites. Univariate analysis was then performed assessing patient length of survival for each primary site subtype. Data was analyzed using SPSS and statistical significance was set at α = 0.05. Results: A total of 9826 patients with known primary site that had survival data were included. The site with the best survival was the lower limb which had significantly better survival than all other primary sites. Tumors of the upper limb had highest median survival (153 months) of those with median survival reported (which was all except for lower limb). Patients with primary tumor of ribs, sternum, clavicle had a significantly better survival than both vertebral column and pelvis/sacrum/coccyx (all p &lt; .01). Upper limb patients survived significantly longer than all groups other than the skull, face, and mandible (p &lt; .05). The labeled primary site with the highest mean survival was the lower limb at 123.1 months and the lowest survival was the pelvis, sacrum, and coccyx, with a median survival of 54.6 months. Conclusions: This study found numerous survival differences between patients diagnosed with OSC of different primary sites. Labeled primary sites of the lower limb and upper limb were associated with best survival while the pelvis, sacrum, and coccyx were associated with worst survival. Future studies should be done to investigate variables that may impact the survival of different primary sites, including staging, treatments, time from diagnosis to treatment, socioeconomic factors, and insurance status.[Table: see text]
The relationship of oncotype Dx Recurrence Score (RS) with Ki 67 in early stage breast cancer patients in a community based cancer center in rural central Nebraska.
Authors: Mehmet Sitki Copur, Tonya Peterson, Soe Min Tun, Adam Horn, Whitney Wedel, Randall Duckert, Nicholas Lintel, Carlene R. Springer, Chandra Muske, Leslie Robbins, Jessica Arbogast, Emily Fakkema, Alison Marshall, Kathryn Brunt, Jacqueline Kelly
Journal: Journal of Clinical Oncology (2022)

e12566 Background: Oncotype Dx recurrence score (RS), is a prognostic and predictive test utilized for decision making in adjuvant therapy of 0-3 node/hormone receptor positive(HR+)/ HER-2-negative early breast cancer. Ki-67 is a marker of proliferating cells and is associated with prognosis and response. Immunohistological (IHC) assessment of Ki 67 expression is less expensive and with the approval of CDK inhibitors in the high risk adjuvant setting, it is increasingly being utilized in clinical decision making. A moderate to strong correlation between Ki67 and Oncotype Dx RS has been reported in the literature. We sought to examine the relationship of Ki 67 to Oncotype Dx RS in a community-based cancer center in rural central Nebraska. Methods: Forty-three consecutive postmenopausal breast cancer patients(pts) diagnosed and treated at our community based cancer center between 2020-2021 with T1–2 N0-1 M0, HR+, HER-2-negative disease were evaluated for histological type, tumor size, Nottingham grade, HR levels, Ki 67 expression (low &lt; 10%, intermediate 10 ≥ Ki67 &lt; 25 high ≥ 25), and Oncotype Dx RS(low &lt;16,intermediate 16⩽RS&lt;26), high ⩾26). Ki 67 and Oncotype Dx RS were treated as continuous variables to calculate a Pearson correlation coefficient. Results: Mean age at diagnosis was 59.4 years (range 48-89). Mean tumor diameter was 15.6 mm. 78.9% were intermediate histologic grade and 9.7% patients had lymph node involvement. Median expression of ER and PR were 90% (5-100) and 70% (0-100), respectively. The mean Ki 67 value was 17.5 (range 5-60 %), and mean Oncotype RS was 14.4 (range 4-34). There was a positive linear correlation between Ki 67 expression and Oncotype Dx RS (Pearson Correlation Coefficient=0.49, P-value &lt;0.001). The vast majority of high Ki 67 pts (80%) had high/intermediate Oncotype RS. All pts with low Ki 67 (100%) had low/intermediate RS. Conclusions: Our community based rural cancer center data support a linear, statistically significant, positive correlation between Ki 67 and Oncotype Dx RS in early stage 0-3 node/HR+ positive breast cancer pts. Increasing use of Ki 67 testing in different clinical settings will generate more data to better define this correlation.[Table: see text]
Development of a remote Mediterranean Diet intervention during chemotherapy treatment: A qualitative analysis.
Authors: Amber Kleckner, Jennifer E Reschke, Lisadine Cherubin, Shari Youngblood, Luke Joseph Peppone
Journal: Journal of Clinical Oncology (2022)

e24033 Background: The Mediterranean Diet (MedDiet) has emerged as an effective health-promoting dietary pattern. It is high in fruit, vegetables, whole grains, fiber, antioxidants, and anti-inflammatory compounds. A cancer diagnosis is often seen as a “window of opportunity” for behavior change, yet there are few structured nutritional programs available for patients undergoing active treatment. Herein, we developed a remote MedDiet intervention and identified barriers and facilitators to adherence. Methods: This was a qualitative analysis of the intervention arm of a clinical trial (NCT04534738). Participants had at least 6 weeks of chemotherapy scheduled. The MedDiet intervention was 8 weeks and included home food delivery (frozen meals and fresh ingredients weekly for the first 4 weeks), education, goal-setting, a cookbook, and weekly phone calls with a nutritionist. MedDiet adherence was measured using the MedDiet Adherence questionnaire at baseline, 4 weeks, and 8 weeks; change was assessed using paired t-tests between baseline and 4 and 8 weeks. After the study, participants underwent a semi-structured interview to provide feedback on the intervention. Interviews were transcribed and emergent coding was used to identify themes. Results: Patients (n = 23) were 52.5±13.6 years old, 2 were male, 83% were White, and 87% had breast cancer. MedDiet adherence was 4.0±2.7 at baseline. It increased 2.1±3.2 points from baseline to 4 weeks and 2.5±3.0 from baseline to 8 weeks (both p &lt; 0.001). Interviews were conducted with 21 patients (example quotes in Table). Although most participants (n = 15, 71%) did not seek nutritional information at the time of their diagnosis, most (n = 19, 90%) were highly engaged with the program. In response to an open-ended question, many (n = 11) expressed a sense of empowerment. Facilitators to adherence included structure, accountability, food provision, palatability, and easy procurement of ingredients. Barriers included chemotherapy-induced taste changes and mouth sores, cooking for family members’ preferences, others preparing food for the patient, and higher priority areas for mental energy expenditure. The majority (n = 13, 62%) preferred a program during vs. after cancer treatment. All (21/21) indicated they would continue to follow at least some aspects of the diet. Conclusions: A remote MedDiet intervention was effective and well received by patients undergoing chemotherapy. Future research should investigate how a MedDiet intervention affects clinical outcomes and symptom burden. Clinical trial information: NCT04534738. [Table: see text]
Assessment of adolescent and young adult oncology patient and provider perspectives in Philadelphia (AYA-4P).
Authors: Christopher Terry, Miriam Pomerantz, Jodi Sandos, Lindsay Wilde
Journal: Journal of Clinical Oncology (2022)

TPS6604 Background: The overall cancer incidence continues to increase in adolescent and young adult patients (AYAs), defined by the National Cancer Institute as individuals diagnosed between the ages of 15-39. Both disease biology and psychosocial needs are unique for young adults living with cancer. AYAs are more likely to have challenges related to work, insurance, relationships, fertility and emotional distress. Studies demonstrate that specialized supportive care improves outcomes such as health-related quality of life, mental health, and physical functioning. Most AYA oncology programs are developed without patient input and affiliated with pediatrics. The Sidney Kimmel Cancer Center (SKCC) at Jefferson is an adult oncology group serving over 900 new patients annually between the ages of 18-39, but does not have a formal AYA program. With guidance from patient advocates and other validated tools, a unique survey-based needs assessment was created by SKCC to provide data for the development of a comprehensive, patient-centered model of care for AYAs. Methods: A one-time survey will be administered electronically to participants through Qualtrics. Solicitation from SKCC and the Young Adult Cancer Connection, a local patient advocacy group, will occur via social media and email aggregation. Eligible patients are those who received the majority of their cancer care within 30 miles of Philadelphia between the ages of 18-39. Eligible healthcare providers include current advanced practice providers or physicians who have practiced at SKCC for at least 1 year. There are no hypotheses being tested or primary outcome variables, therefore no sample size calculations were performed. A $10 Amazon card is offered as incentive for the patient-directed survey to improve response rates and reach at least 100 completed surveys. The provider survey includes no completion incentive. Each survey should take no longer than 20 minutes to complete and no follow-up is required. Surveys are multiple choice with a single open-ended, free response question at the end for additional comments. Categorical survey responses will be summarized using frequencies and percentages. Descriptive statistics and data visualization will be used to characterize the patient demographics and summarize awareness, experiences, and priorities of the participants. Primary objectives of the surveys are to assess AYAs’ current perspective of age-specific medical services and psychosocial support in Philadelphia, as well as to assess the knowledge and perspective of providers of the current care and available services for AYAs at SKCC. The secondary objective is to identify patient preferences and areas for improvement. By using the data generated from the surveys, SKCC will be more informed in their patient-centric approach to program development in an effort to improve the overall care for Philadelphia’s AYA oncology community.
The use of ARMCan app to improve the quality of life in breast cancer patients with chemobrain.
Authors: Abigail N. Koehler, Yehudit Rothman, Diego Gomez Enriquez, Michelle Kirschner, Rhonna Shatz, Abdelkader Mahammedi, Claudia B. Rebola, Soma Sengupta
Journal: Journal of Clinical Oncology (2022)

e13619 Background: Breast cancer is the most diagnosed cancer in women with approximately 2 million women diagnosed in 2018. The 10-year survival rate is 78%. Breast cancer patients who undergo chemotherapy treatment can suffer neurocognitive impairment resulting in significant effects on their cognitive functioning. Chemotherapy-related dysfunction is known as “chemobrain”. Chemobrain is the basis of significant neurological morbidities in the breast cancer population. It causes difficulty in people being able to carry out activities of daily living and impacts people’s livelihoods and well-being. Studies have shown that music-based intervention can improve cognitive function. Methods: Since music-based interventions to specifically address chemo-related cognitive deficits have not been explored, we are conducting a pilot feasibility study to beta test the novel Active Receptive Music for Cancer patients application (ARMCan) which allows its user to have an interactive musical experience. Patients are randomized into two arms. In receptive listening, users listen to a genre of their choice, and in active listening, users add sounds over a base trace. At the beginning of the study, patients will be given a FACT-Cog questionnaire and undergo MRI imaging. The study invention will be conducted for six months where patients will use the ARMCan app for 15 minutes daily. They will be followed for one year post-study intervention with FACT-Cog questionnaires given directly after the cessation of the study intervention and at months six and 12 of follow up. An additional MRI will be taken at month 12 of follow up. Results: FACT-Cog and MRI data will be used to analyze the results of active versus receptive music therapy on chemotherapy-related cognition dysfunction. Conclusions: We are currently accruing patients to beta test this interactive application, which may promote executive function recovery in breast cancer patients with chemobrain and advance clinical care in breast cancer survivorship.
Retrospective review of glioma patients with confirmed MET amplification or fusion.
Authors: Ramya Tadipatri, Adela Miller, Chukwuyem Ekhator, Manmeet Singh Ahluwalia, Jai Grewal, Ekokobe Fonkem
Journal: Journal of Clinical Oncology (2022)

e14029 Background: The MET pathway is a key oncogenic pathway in gliomas and is involved in tumor survival, angiogenesis, and invasion. MET alterations have been increasingly identified as a potential therapeutic target. Methods: Our objective was to further characterize the natural history of gliomas which harbor MET alterations and study outcomes as determined by progression free survival (PFS) and overall survival (OS). Results: We identified 22 glioma patients seen at our institution between 2015 and 2021 who had a MET alteration confirmed through comprehensive molecular profiling. There were 18 grade 4 astrocytomas/glioblastomas, 3 grade 3 gliomas (2 astrocytomas, 1 oligodendroglioma), and 1 grade 2 glioma (oligodendroglioma). MET amplification was observed in 13 patients and fusion in 16 patients, with 7 patients carrying both amplification and fusion alterations. MET fusion partners included PTPRZ1 (8 patients), CAPZA2 (6 patients), and ST7 (3 patients). Median OS was 12.8 months, and median PFS was 8.47 months. IDH1/2 mutation was associated with significantly improved survival, with an estimated OS of 146 months for IDH1/2 mutant tumors and 17.9 months for IDH1/2 wildtype tumors (F 2,2 = 38.907, p &lt; 0.001), MGMT methylation status had no significant survival impact. No significant survival differences were observed between the fusion only, amplification only, and combined fusion and amplification groups. No therapy was predictive of improved outcomes. Conclusions: MET amplification and fusion alterations were observed in both low and high grade gliomas, suggesting that they may be involved in early tumorigenesis. Survival outcomes were poor compared with historical data, with no differences observed between treatment groups, suggesting that current therapeutic modalities may be inadequate. This study indicates that MET may be an appropriate therapeutic target, laying the groundwork for clinical trials investigating MET-targeted agents.
Homologous recombination deficiency (HRD) alterations as a predictor of responsiveness to combination pancreatic cancer in advanced pancreatic ductal adenocarcinoma (PDAC).
Authors: Jamie Randall, Timothy Lewis Cannon, Raymond Couric Wadlow, Hongkun Wang, Arthur Winer
Journal: Journal of Clinical Oncology (2022)

e16259 Background: Advanced PDAC is associated with a poor prognosis and median survivals of less than one year. FOLFIRINOX and Gemcitabine/Nab-Paclitaxel are both considered standard of care in the first line setting, though there is considerable variability among oncologists regarding sequencing of these regimens. Pre-clinical and clinical data support the use of platinum therapy in HRD+ PDAC, but little is known about how this translates into best practices regarding sequencing of treatment or clinical benefit relevant to Gemcitabine based therapies in this population. Methods: Using the cancer registry and Inova molecular tumor board database, we retrospectively reviewed all patients from January 2015 until November 2021 with unresectable PDAC who had NGS performed and stratified by the presence or absence of HRD mutation. HRD mutations included by BRCA1, BRCA2, PALB2, ATM, ATR, CHEK2, ARID1A, FANCA, FANCL. We analyzed for RR to Folfirinox/Folfox and Gemcitabine based therapies, adjusted time to progression on Folfirinox/Folfox (time from first dose of oxaliplatin based combination to first dose of gemcitabine to account for those who stopped oxaliplatin early for neuropathy or received maintenance therapy), and time on gemcitabine based therapy. Results: 142 consecutive patients with advanced PDAC were examined, including 20 with HRD variants. When excluding those who eventually received surgery and those who never received platinum therapy, we were left with 87 (74 in Control and 13 in HRD) for analysis. RR to Folfirinox/Folfox was 60% in HRD+ and 31.25% in control (p = 0.71) (Table). Mean adjusted time to progression on Folfirinox/Folfox was 320.0 days in HRD+ group and 252.9 in the control group (p = 0.57) (Table 2). The time on treatment for gemcitabine based combination therapy was 260.7 in HRD+ and 165.1 in control group. Conclusions: HRD+ patients had longer durations of treatment on both 5-FU based therapy and Gemcitabine based combinations. These data challenges the importance of first line platinum therapy in HRD+ patients, and further exploration should be considered.[Table: see text]
Relationship between IFN-α, IL-1B, IL-5, IL-6 and effectiveness of the first-line with camrelizumab combined with chemotherapy in non small cell lung cancer.
Authors: Jian Shi, Xiaoyang Duan, Rongfeng Liu, Zhen Wang, Shan Han, Baoen Shan
Journal: Journal of Clinical Oncology (2022)

e21059 Background: Biomarkers of combination with immunotherapy therapy remains unknown. To explore prediction of efficacy in patients(pts) with non small cell lung cancer (NSCLC) without driver genes mutations which received Camrelizumab combined with chemotherapy. Methods: From Jan, 2020 to Dec, 2021, 28 pts with NSCLC without driver genes mutations who received Camrelizumab combined with chemotherapy for 4 cycles. According to RECIST1.1, all of these patients were assessed with benefit. IFN, TNF-α, IL (IL-1B、IL-2、IL-4、IL5、IL-6、IL-8、IL-10、IL-12P70、IL-17)in peripheral blood of all pts were measured using flow cytometry. Statistical analyses were performed with SPSS 23.0 software (Pearson’s correlation). Results: Before treatment, the mean values of IFN-α, IFN-γ, TNF-α and IL in pts with partial response (PR) were higher than in pts with stable disease (SD). There was no correlation with age, sex, stage and pathological type of pts ( P &gt; 0.05). There was significant difference of IFN- α, IL-1B, IL-5 and IL-6 increased compared with the level before treatment in 28 pts ( P＜0.05). However, pts with PR compared with pts with SD, There were no significant differences of IFN-α, IFN-γ, TNF-α, IL compared with the level before treatment (P &gt; 0.05). The IFN-α, IL-1B, IL-5, IL-6 Spearman correlation showed that before treatment, there was a correlation between INF-α and IL-5, INF-α and IL-1B, INF- α and IL-6, IL-1B and IL-6, respectively (r = 0.786, P = 0.036 &lt; 0.05; r = 0.889, P = 0.007 &lt; 0.05; r = 0.929, P = 0.003 &lt; 0.05; r = 0.778, P = 0.039 &lt; 0.05). In self-control before and after treatment, there was a correlation between INF-α and IL-1B, INF- α and IL-6, IL-1B and IL-6, respectively (r = 0.880, P = 0.009 ＜05; r = 0.936, P = 0.002＜ 0.05; r = 0.882, P = 0.023＜ 0.05). Conclusions: First-line chemotherapy combined with Camrelizumab in NSCLC without driver genes mutations can effectively improve the levels of IFN-α, IL-1B, IL-5, and IL-6, and the combined detection has certain predictive significance for the efficacy evaluation of patients. Further study is needed.